The major objectives of the proposed research are to determine the cause of and to find effective treatments for nephrolithiasis (Ca- containing), osteoporosis and osteomalacia. The crystal nidus for the calcium-containing renal stones is brushite. Renal stones probably form from the persistent passage of urine supersaturated with respect to brushite, particularly when the state of saturation exceeds the formation product of brushite. Conversely, renal stones cannot form when the state of saturation is below the formation product. The proposed study will utilize this criteria to evaluate objectively various methods of treatment. Since hypercalciuria is the major determinant for the state of supersaturation, the exact mechanism for its development and drugs to abate it will be sought. In particular, the effects of cellulose phosphate, hydrochlorothiazide, methylene blue and diphosphonate will be examined. Idiopathic osteoporosis may result from an inappropriate secretion of parathyroid hormone. The proposed study will analyze the factors controlling the secretion of PTH, and consider the hormonal consequences of and the therapeutic value of repeated calcium infusions. In particular, the effects of treatment on the plasma concentration of PTH and on the density of bone will be examined. The biochemical defect in osteomalacia and familial hypophosphatemia is probably the impairment in the metabolism of vitamin D. The 25-hydroxycholecalciferol has been shown to correct some forms of vitamin D resistance. The proposed study will consider the physiological actions and the thereapeutic value of vitamin D metabolites. Finally, the role of the organic matrix in the formation of bone and of renal stones will be examined.